The object of this project is to examine the regulation of gene expression during neoplastic progression as well as during the noraml growth and differentiation process. Our aim is to identify and characterize both cellular and genetic factors that are of critical importance in the oncogenic process. The experimental systems presently under study are (A)\the human promyelocytic leukemia cell line, HL60; (B) a variety of undifferentiated human B cells and B-cell lymphomas; and (C) the rat hepatoma cell line and primary hepatocytes. The results obtained in the HL60 cell line study include (1) functional association of c-myc expression with the differentiated state of the cell, and (2) expression of the 2.2 kb N-ras specific transcript associated to some extent with the proliferative capacity of the cells. The results obtained and the experiments in progress in the human B-cell study include (1) chemical transformation of lymphoblastoid cell lines into high grade lymphomas, (2) transformation of NIH 3T3 cells by transfection of DNA obtained from these high grade lymphomas, (3) analysis of the transfection specific gene, and (4)\two-dimensional gel analysis of proteins associated with the chemically-induced transformation state. The results obtained and the experiments in progress in the rat hepatoma and primary hepatocyte study include (1) partial construction of cDNA libraries which correspond to discrete stages in the neoplastic progression of rat hepatomas, (2)\isolation of cDNA recombinant clones which are up-regulated in actively proliferating rat liver (i.e., following partial hepatectomy) as compared to normal adult liver, and (3) characterization of the change in expression of a differentiation specific gene.